tbuckley/cabot-search huggingface dataset:
A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke
Authors: Patrick D. Lyden, Márcio A. Diniz, Francesca Bosetti, Jessica Lamb, Karisma A. Nagarkatti, André Rogatko, Sungjin Kim, Ryan P. Cabeen, James I. Koenig, Kazi Akhter, Ali S. Arbab, Brooklyn D. Avery, Hannah E. Beatty, Adnan Bibic, Suyi Cao, Ligia Simoes Braga Boisserand, Angel Chamorro, Anjali Chauhan, Sebastian Diaz-Perez, Krishnan Dhandapani, Nirav Dhanesha, Andrew Goh, Alison L. Herman, Fahmeed Hyder, Takahiko Imai, Conor W. Johnson, Mohammad B. Khan, Pradip Kamat, Senthilkumar S. Karuppagounder, Mariia Kumskova, Jelena M. Mihailovic, Joseph B. Mandeville, Andreia Morais, Rakesh B. Patel, Basavaraju G. Sanganahalli, Cameron Smith, Yanrong Shi, Brijesh Sutariya, Daniel Thedens, Tao Qin, Sofia E. Velazquez, Jaroslaw Aronowski, Cenk Ayata, Anil K. Chauhan, Enrique C. Leira, David C. Hess, Raymond C. Koehler, Louise D. McCullough, Lauren H. Sansing
Journal: Science Translational Medicine (2023)

Human diseases may be modeled in animals to allow preclinical assessment of putative new clinical interventions. Recent, highly publicized failures of large clinical trials called into question the rigor, design, and value of preclinical assessment. We established the Stroke Preclinical Assessment Network (SPAN) to design and implement a randomized, controlled, blinded, multi-laboratory trial for the rigorous assessment of candidate stroke treatments combined with intravascular thrombectomy. Efficacy and futility boundaries in a multi-arm multi-stage statistical design aimed to exclude from further study highly effective or futile interventions after each of four sequential stages. Six independent research laboratories performed a standard focal cerebral ischemic insult in five animal models that included equal numbers of males and females: young mice, young rats, aging mice, mice with diet-induced obesity, and spontaneously hypertensive rats. The laboratories adhered to a common protocol and efficiently enrolled 2615 animals with full data completion and comprehensive animal tracking. SPAN successfully implemented treatment masking, randomization, prerandomization inclusion and exclusion criteria, and blinded assessment of outcomes. The SPAN design and infrastructure provide an effective approach that could be used in similar preclinical, multi-laboratory studies in other disease areas and should help improve reproducibility in translational science.
The D2D3 form of uPAR acts as an immunotoxin and may cause diabetes and kidney disease
Authors: Ke Zhu, Kamalika Mukherjee, Changli Wei, Salim S. Hayek, Agnieszka Collins, Changkyu Gu, Kristin Corapi, Mehmet M. Altintas, Yong Wang, Sushrut S. Waikar, Antonio C. Bianco, Alexander Koch, Frank Tacke, Jochen Reiser, Sanja Sever
Journal: Science Translational Medicine (2023)

Soluble urokinase plasminogen activator receptor (suPAR) is a risk factor for kidney diseases. In addition to suPAR, proteolysis of membrane-bound uPAR results in circulating D1 and D2D3 proteins. We showed that when exposed to a high-fat diet, transgenic mice expressing D2D3 protein developed progressive kidney disease marked by microalbuminuria, elevated serum creatinine, and glomerular hypertrophy. D2D3 transgenic mice also exhibited insulin-dependent diabetes mellitus evidenced by decreased levels of insulin and C-peptide, impaired glucose-stimulated insulin secretion, decreased pancreatic β cell mass, and high fasting blood glucose. Injection of anti-uPAR antibody restored β cell mass and function in D2D3 transgenic mice. At the cellular level, the D2D3 protein impaired β cell proliferation and inhibited the bioenergetics of β cells, leading to dysregulated cytoskeletal dynamics and subsequent impairment in the maturation and trafficking of insulin granules. D2D3 protein was predominantly detected in the sera of patients with nephropathy and insulin-dependent diabetes mellitus. These sera inhibited glucose-stimulated insulin release from human islets in a D2D3-dependent manner. Our study showed that D2D3 injures the kidney and pancreas and suggests that targeting this protein could provide a therapy for kidney diseases and insulin-dependent diabetes mellitus.
Artificial Intelligence and Diabetic Retinopathy: AI Framework, Prospective Studies, Head-to-head Validation, and Cost-effectiveness
Authors: Anand E. Rajesh, Oliver Q. Davidson, Cecilia S. Lee, Aaron Y. Lee
Journal: Diabetes Care (2023)

Current guidelines recommend that individuals with diabetes receive yearly eye exams for detection of referable diabetic retinopathy (DR), one of the leading causes of new-onset blindness. For addressing the immense screening burden, artificial intelligence (AI) algorithms have been developed to autonomously screen for DR from fundus photography without human input. Over the last 10 years, many AI algorithms have achieved good sensitivity and specificity (&amp;gt;85%) for detection of referable DR compared with human graders; however, many questions still remain. In this narrative review on AI in DR screening, we discuss key concepts in AI algorithm development as a background for understanding the algorithms. We present the AI algorithms that have been prospectively validated against human graders and demonstrate the variability of reference standards and cohort demographics. We review the limited head-to-head validation studies where investigators attempt to directly compare the available algorithms. Next, we discuss the literature regarding cost-effectiveness, equity and bias, and medicolegal considerations, all of which play a role in the implementation of these AI algorithms in clinical practice. Lastly, we highlight ongoing efforts to bridge gaps in AI model data sets to pursue equitable development and delivery.
Integrated epigenetic and transcriptional single-cell analysis of t(11;14) multiple myeloma and its BCL2 dependency
Authors: Noémie Leblay, Sungwoo Ahn, Rémi Tilmont, Mansour Poorebrahim, Ranjan Maity, Holly Lee, Elie Barakat, Jean-Baptiste Alberge, Sarthak Sinha, Arzina Jaffer, Benjamin G. Barwick, Lawrence H. Boise, Nizar Bahlis, Paola Neri
Journal: Blood (2023)

The translocation t(11;14) occurs in 20% of patients with multiple myeloma (MM) and results in the upregulation of CCND1. Nearly two-thirds of t(11;14) MM cells are BCL2 primed and highly responsive to the oral BCL2 inhibitor venetoclax. Although it is evident that this unique sensitivity to venetoclax depends on the Bcl-2 homology domain 3- proapoptotic protein priming of BCL2, the biology underlying t(11;14) MM dependency on BCL2 is poorly defined. Importantly, the epigenetic regulation of t(11;14) transcriptomes and its impact on gene regulation and clinical response to venetoclax remain elusive. In this study, by integrating assay for transposase-accessible chromatin by sequencing (ATAC-seq) and RNA-seq at the single-cell level in primary MM samples, we have defined the epigenetic regulome and transcriptome associated with t(11;14) MM. A B-cell-like epigenetic signature was enriched in t(11;14) MM, confirming its phylogeny link to B-cell rather than plasma cell biology. Of note, a loss of a B-cell-like epigenetic signature with a gain of canonical plasma cell transcription factors was observed at the time of resistance to venetoclax. In addition, MCL1 and BCL2L1 copy number gains and structural rearrangements were linked to venetoclax resistance in patients with t(11;14) MM. To date, this is the first study in which both single-cell (sc) ATAC-seq and scRNA-seq analysis are integrated into primary MM cells to obtain a deeper resolution of the epigenetic regulome and transcriptome associated with t(11;14) MM biology and venetoclax resistance.
Shear-Wave Elastography Reflects Myocardial Stiffness Changes in Pediatric Inflammatory Syndrome Post COVID-19
Authors: Ahmed S. Youssef, Thomas Salaets, Stéphanie Bézy, Laurine Wouters, Marta Orlowska, Annette Caenen, Jürgen Duchenne, Alexis Puvrez, Lien De Somer, Bjorn Cools, Jan D’hooge, Marc Gewillig, Jens-Uwe Voigt
Journal: JACC. Cardiovascular imaging (2023)
Comparison Between Acoustic Radiation Force-Induced and Natural Wave Velocities for Myocardial Stiffness Assessment in Hypertrophic Cardiomyopathy
Authors: Aimen Malik, Jose Carlos Villalobos Lizardi, Jerome Baranger, Maelys Venet, Mathieu Pernot, Seema Mital, Minh Bao Nguyen, Rajiv Chaturvedi, Luc Mertens, Olivier Villemain
Journal: JACC. Cardiovascular imaging (2023)
Tricuspid Regurgitation
Authors: Julia Grapsa, Fabien Praz, Paul Sorajja, Joao L Cavalcante, Marta Sitges, Maurizio Taramasso, Nicolo Piazza, David Messika-Zeitoun, Hector I Michelena, Nadira Hamid, Julien Dreyfus, Giovanni Benfari, Edgar Argulian, Alaide Chieffo, Didier Tchetche, Lawrence Rudski, Jeroen J Bax, Ralph Stephan von Bardeleben, Tiffany Patterson, Simon Redwood, Vinayak N Bapat, Georg Nickenig, Philipp Lurz, Jörg Hausleiter, Susheel Kodali, Rebecca T Hahn, Francesco Maisano, Maurice Enriquez-Sarano
Journal: JACC. Cardiovascular imaging (2023)
Reply
Authors: Paul Leong, James H. Hull, Peter G. Gibson, Thomas Halvorsen, Philip G. Bardin, Anne E. Vertigan, Vanessa M. McDonald, Mark Hew, Malcolm Baxter, Debra Phyland, Thomas L. Carroll, Hege Havstad Clemm, Maria Vollsæter, Ola Drange Røksund
Journal: Journal of Allergy and Clinical Immunology (2023)
Redefining the non-communicable disease framework to a 6 × 6 approach: incorporating oral diseases and sugars
Authors: Habib Benzian, Abdallah Daar, Sudeshni Naidoo
Journal: The Lancet Public Health (2023)

The WHO Global Oral Health Status Report, published in 2022, highlighted the alarming state of oral health worldwide and called for urgent action by integrating oral health into non-communicable diseases (NCDs) and universal health coverage initiatives. 3·5 billion people have oral diseases, surpassing all other NCDs combined. The detrimental role of sugars as a risk factor for oral diseases and other NCDs has also been well documented. Despite the evidence, oral diseases and sugars are not part of the current NCD framing, which focuses on five diseases and five risk factors (ie, 5 × 5). Oral diseases and sugars remain sidelined, disproportionately affecting poor and disadvantaged populations. In this Viewpoint, we advocate for the integration of oral diseases and sugars into the current approach towards the prevention and control of NCDs. An expanded 6 × 6 framework would recognise growing evidence and would reiterate the need to strengthen action, resource allocation, and policy development for NCDs. We present the evidence and rationale for, and benefits of, an expanded NCD framework and detail recommendations to guide efforts towards improved priority, investment, and equitable health outcomes for NCDs, including oral health.
Multi-Cancer Early Detection: The New Frontier in Cancer Early Detection
Authors: Carmen E. Guerra, Prateek V. Sharma, Brenda S. Castillo
Journal: Annual Review of Medicine (2023)

The new generation of cancer early detection tests holds remarkable promise for revolutionizing and changing the paradigm of cancer early detection. Dozens of cancer early detection tests are being developed and evaluated. Some are already commercialized and available for use, most as a complement to and not in place of existing recommended cancer screening tests. This review evaluates existing single- and multi-cancer early detection tests (MCEDs), discussing their performance characteristics including sensitivity, specificity, positive and negative predictive values, and accuracy. It also critically looks at the potential harms that could result from these tests, including false positive and negative results, the risk of overdiagnosis and overtreatment, psychological and economic harms, and the risk of widening cancer inequities. We also review the large-scale, population-based studies that are being launched in the United States and United Kingdom to determine the impact of MCEDs on clinically relevant outcomes and implications for current practice.
Decoding Human Biology and Disease Using Single-Cell Omics Technologies
Authors: Qiang Shi, Xueyan Chen, Zemin Zhang
Journal: Genomics Proteomics & Bioinformatics (2023)

Abstract Over the past decade, advances in single-cell omics (SCO) technologies have enabled the investigation of cellular heterogeneity at an unprecedented resolution and scale, opening a new avenue for understanding human biology and disease. In this review, we summarize the developments of sequencing-based SCO technologies and computational methods, and focus on considerable insights acquired from SCO sequencing studies to understand normal and diseased properties, with a particular emphasis on cancer research. We also discuss the technological improvements of SCO and its possible contribution to fundamental research of the human, as well as its great potential in clinical diagnoses and personalized therapies of human disease.
Human macrophage migration inhibitory factor potentiates mesenchymal stromal cell efficacy in a clinically relevant model of allergic asthma
Authors: Ian J. Hawthorne, Hazel Dunbar, Courteney Tunstead, Tamara Schorpp, Daniel J. Weiss, Sara Rolandsson Enes, Claudia C. dos Santos, Michelle E. Armstrong, Seamas C. Donnelly, Karen English
Journal: Molecular Therapy (2023)
CXCR4-modified CAR-T cells suppresses MDSCs recruitment via STAT3/NF-κB/SDF-1α axis to enhance efficacy against pancreatic cancer
Authors: Ruixin Sun, Yansha Sun, Chuanlong Wu, Yifan Liu, Min Zhou, Yiwei Dong, Guoxiu Du, Hong Luo, Bizhi Shi, Hua Jiang, Zonghai Li
Journal: Molecular Therapy (2023)

Claudin18.2 (CLDN18.2)-specific chimeric antigen receptor (CAR-T) cells displayed limited efficacy in CLDN18.2-positive pancreatic ductal adenocarcinoma (PDAC). Strategies are needed to improve the trafficking capacity of CLDN18.2-specific CAR-T cells. PDAC has a unique microenvironment that consists of abundant cancer-associated fibroblasts (CAFs), which could secrete stromal cell-derived factor 1α (SDF-1α), the ligand of CXCR4. Then, we constructed and explored CLDN18.2-targeted CAR-T cells with CXCR4 co-expression in treating immunocompetent mouse models of PDAC. The results indicated that CXCR4 could promote the infiltration of CAR-T cells and enhance their efficacy in vivo. Mechanistically, the activation of signal transducer and activator of transcription 3 (STAT3) signaling was impaired in CXCR4 CAR-T cells, which reduced the release of inflammatory factors, such as tumor necrosis factor-α, IL-6, and IL-17A. Then, the lower release of inflammatory factors suppressed SDF-1α secretion in CAFs via the nuclear factor κB (NF-κB) pathway. Therefore, the decreased secretion of SDF-1α in feedback decreased the migration of myeloid-derived suppressor cells (MDSCs) in tumor sites. Overall, our study demonstrated that CXCR4 CAR-T cells could traffic more into tumor sites and also suppress MDSC migration via the STAT3/NF-κB/SDF-1α axis to obtain better efficacy in treating CLDN18.2-positive pancreatic cancer. Our findings provide a theoretical rationale for CXCR4 CAR-T cell therapy in PDAC.
Optimal delivery of RNA interference by viral vectors for cancer therapy
Authors: Boaz Wong, Rayanna Birtch, Reza Rezaei, Taylor Jamieson, Mathieu J.F. Crupi, Jean-Simon Diallo, Carolina S. Ilkow
Journal: Molecular Therapy (2023)

In recent years, there has been a surge in the innovative modification and application of the viral vector-based gene therapy field. Significant and consistent improvements in the engineering, delivery, and safety of viral vectors have set the stage for their application as RNA interference (RNAi) delivery tools. Viral vector-based delivery of RNAi has made remarkable breakthroughs in the treatment of several debilitating diseases and disorders (e.g., neurological diseases); however, their novelty has yet to be fully applied and utilized for the treatment of cancer. This review highlights the most promising and emerging viral vector delivery tools for RNAi therapeutics while discussing the variables limiting their success and suitability for cancer therapy. Specifically, we outline different integrating and non-integrating viral platforms used for gene delivery, currently employed RNAi targets for anti-cancer effect, and various strategies used to optimize the safety and efficacy of these RNAi therapeutics. Most importantly, we provide great insight into what challenges exist in their application as cancer therapeutics and how these challenges can be effectively navigated to advance the field.
Development of the Generalized Pustular Psoriasis Clinical Assessment Tool
Authors: Amit Garg, Megan H. Noe, Milan J. Anadkat, April Armstrong, Tina Bhutani, Aaron Farberg, George Han, Jason E. Hawkes, Mark Lebwohl, Sergey Rekhtman, Eingun J. Song, Andrew Strunk, Kristina C. Duffin
Journal: Journal of the American Academy of Dermatology (2023)
Targeting PRMT1 prevents acute and chronic graft-versus-host disease
Authors: Xiaoyan Zhao, Yan Sun, Ziwei Xu, Li Cai, Yu Hu, Huafang Wang
Journal: Molecular Therapy (2023)

Graft-versus-host disease (GVHD) is a common complication after allogeneic hematopoietic stem cell transplantation. Recent studies have reported that protein arginine methyltransferase 1 (PRMT1) is essential for the differentiation and proliferation of T and B cells. Therefore, it is possible that PRMT1 may play a critical role in GVHD. In this study, we observed that PRMT1 expression was upregulated in CD4
Real-world effectiveness of risankizumab in patients with moderate-to-severe psoriasis using the CorEvitas Psoriasis Registry
Authors: Bruce Strober, Laura Ferris, Kristina Callis Duffin, Jud C. Janak, Adam P. Sima, Thomas Eckmann, Manish Patel, Huzefa Photowala, Vishvas Garg, April Armstrong
Journal: Journal of the American Academy of Dermatology (2023)

Psoriasis, an inflammatory skin disease, is often treated with biologic therapeutics.
The Evolving Practice of Hospital at Home in the United States
Authors: Tuyet-Trinh Truong, Albert L. Siu
Journal: Annual Review of Medicine (2023)

Hospital at Home (HaH) provides hospital-level services in the home to eligible patients who would otherwise require facility-based hospitalization. In the last two decades, studies have shown that HaH can improve patient outcomes and satisfaction and reduce hospital readmissions. Improved technology and greater experience with the model have led to expansion in the scope of patients served and services provided by the model, but dissemination in the United States has been hampered by lack of insurance coverage until recently. HaH is likely at the tipping point for wide adoption in the United States. To realize its full benefits, HaH will need to continue volume expansion to achieve culture change in clinical practice as facilitated by increased insurance coverage, technological advancements, and improved workforce expertise. It is also essential that HaH programs maintain high-quality acute hospital care, ensure that their benefits can be accessed by hard-to-reach rural populations, and continue to advance health equity.
Effect Modifications of Overhead-View and Eye-Level Urban Greenery on Heat–Mortality Associations: Small-Area Analyses Using Case Time Series Design and Different Greenery Measurements
Authors: Jinglu Song, Antonio Gasparrini, Thomas Fischer, Kejia Hu, Yi Lu
Journal: Environmental Health Perspectives (2023)

Background: The protective effect of urban greenery from adverse heat impacts remains inconclusive. Existing inconsistent findings could be attributed to the different estimation techniques used. Objectives: We investigated how effect modifications of urban greenery on heat–mortality associations vary when using different greenery measurements reflecting overhead-view and eye-level urban greenery. Methods: We collected meteorological and daily mortality data for 286 territory planning units between 2005 and 2018 in Hong Kong. Three greenery measurements were extracted for each unit: a) the normalized difference vegetation index (NDVI) from Landsat remote sensing images, b) the percentage of greenspace based on land use data, and c) eye-level street greenery from street view images via a deep learning technique. Time-series analyses were performed using the case time series design with a linear interaction between the temperature term and each of the three greenery measurements. Effect modifications were also estimated for different age groups, sex categories, and cause-specific diseases. Results: Higher mortality risks were associated with both moderate and extreme heat, with relative risks (RRs) of 1.022 (95% CI: 1.000, 1.044) and 1.045 (95% CI: 1.013, 1.079) at the 90th and 99th percentiles of temperatures relative to the minimum mortality temperature (MMT). Lower RRs were observed in greener areas whichever of the three greenery measurements was used, but the disparity of RRs between areas with low and high levels of urban greenery was more apparent when using eye-level street greenery as the index at high temperatures (99th percentile relative to MMT), with RRs for low and high levels of greenery, respectively, of 1.096 (95% CI: 1.035, 1.161) and 0.985 (95% CI: 0.920, 1.055) for NDVI (p=0.0193), 1.068 (95% CI: 1.021, 1.117) and 0.990 (95% CI: 0.906, 1.081) for the percentage of greenspace (p=0.1338), and 1.103 (95% CI: 1.034, 1.177) and 0.943 (95% CI: 0.841, 1.057) for eye-level street greenery (p=0.0186). Health discrepancies remained for nonaccidental mortality and cardiorespiratory diseases and were more apparent for older adults (≥65 years of age) and females. Discussion: This study provides new evidence that eye-level street greenery shows stronger associations with reduced heat–mortality risks compared with overhead-view greenery based on NDVI and percentage of greenspace. The effect modification of urban greenery tends to be amplified as temperatures rise and are more apparent in older adults and females. Heat mitigation strategies and health interventions, in particular with regard to accessible and visible greenery, are needed for helping heat-sensitive subpopulation groups in coping with extreme heat. https://doi.org/10.1289/EHP12589
Ketamine: Mechanisms and Relevance to Treatment of Depression
Authors: Ji-Woon Kim, Kanzo Suzuki, Ege T. Kavalali, Lisa M. Monteggia
Journal: Annual Review of Medicine (2023)

Major depressive disorder (MDD) is a leading cause of suicide in the world. Monoamine-based antidepressant drugs are a primary line of treatment for this mental disorder, although the delayed response and incomplete efficacy in some patients highlight the need for improved therapeutic approaches. Over the past two decades, ketamine has shown rapid onset with sustained (up to several days) antidepressant effects in patients whose MDD has not responded to conventional antidepressant drugs. Recent preclinical studies have started to elucidate the underlying mechanisms of ketamine's antidepressant properties. Herein, we describe and compare recent clinical and preclinical findings to provide a broad perspective of the relevant mechanisms for the antidepressant action of ketamine.
Sources of Low-Value Care Received by Medicare Beneficiaries and Associated Spending Within US Health Systems
Authors: Emma D. Chant, Maia Crawford, Ching-Wen Wendy Yang, Elliott S. Fisher, Nancy E. Morden, Ishani Ganguli
Journal: JAMA Network Open (2023)

This cross-sectional study examines referrals for low-value health care services and associated spending by ordering clinician among Medicare beneficiaries.
Consumption of Ultraprocessed Food and Risk of Depression
Authors: Chatpol Samuthpongtorn, Long H. Nguyen, Olivia I. Okereke, Dong D. Wang, Mingyang Song, Andrew T. Chan, Raaj S. Mehta
Journal: JAMA Network Open (2023)

This cohort study examines the consumption of ultraprocessed food and risk of depression among 31 172 US females aged 42 to 62 years.